Exhaled breath condensate (EBC) pH reflects the acid-base homeostasis of the airway lining fluid and is up to 3 log order lower in various inflammatory lung diseases including asthma, COPD, bronchiectasis, and cystic fibrosis (CF) than in normal controls. The aim of this study was to confirm this finding in CF and determine if there was a significant change in EBC pH after treatment of an acute pulmonary exacerbation. Ten subjects with CF and a pulmonary exacerbation, and 10 healthy age-matched control subjects were studied. EBC was collected at the onset of an acute pulmonary exacerbation and after treatment with intravenous antibiotics (median duration: 14 days (interquartile range, IQR): 12-14) when the exacerbation was considered resolved. The median age for CF patients was 15.9 years (IQR: 13-18.8), compared to 18 years (IQR: 15-24.8) for the control group, P = 0.242. All CF subjects had severe lung disease, median FEV(1) = 41.5% of predicted (IQR: 30.8-46.5%). Median EBC pH in CF subjects at the onset of a pulmonary exacerbation was 6.61 (IQR: 6.17-7.91) compared to median EBC pH of 8.14 (IQR: 7.45-9.08) in the control group, P < 0.02. Median EBC pH after resolution of an exacerbation was 7.02 (IQR: 5.8-8.64), not significantly different (P = 0.667) than during the acute exacerbation. EBC pH decreased in five subjects, increased in three subjects and there was no change in two subjects. There was no correlation between EBC pH and FEV(1) either before or after intravenous antibiotics. EBC ammonia, an important buffer of ASL, was also measured and similarly found to be lower than in normal controls. EBC pH is lower in CF than age-matched controls, and did not change consistently in response to treatment of an acute pulmonary exacerbation.